Al-Eitan Laith N, Al-Dalala Islam M, Elshammari Afrah K, Khreisat Wael H, Nimiri Aseel F, Alnaamneh Adan H, Aljamal Hanan A, Alghamdi Mansour A
Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan.
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.
Pharmgenomics Pers Med. 2020 Oct 16;13:503-510. doi: 10.2147/PGPM.S273125. eCollection 2020.
The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients.
A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis.
The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness.
Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).
本研究旨在调查溶质载体家族1成员1（SLC1A1）、溶质载体家族6成员1（SLC6A1）、家族性131B成员（FAM131B）、糖基磷脂酰肌醇特异性磷脂酶D1（GPLD1）、凝血因子Ⅱ（F2）、γ-氨基丁酸A型受体γ2亚基（GABRG2）、γ-氨基丁酸A型受体α1亚基（GABRA1）和电压门控性钙通道辅助亚基5（CACNG5）基因内的单核苷酸多态性（SNP）对约旦患者抗癫痫药物（AED）反应及癫痫遗传易感性的可能影响。
招募了来自约旦人群的299名健康个体和296名儿科患者。采集血样，并使用定制平台阵列分析进行基因分型。
发现SLC1A1基因的rs10815018和FAM131B基因的rs4236482多态性与癫痫易感性相关。此外，SLC1A1基因的rs10815018和GPLD1基因的rs1126617多态性与全身性癫痫（GE）相关，而FAM131B基因的rs4236482与局灶性表型相关。关于治疗反应，FAM131B基因的rs4236482、GABRA1基因的rs2279020和CACNG5基因的rs740805的基因多态性导致对AEDs反应不佳（耐药）。GLPD1单倍型与癫痫、其亚型及治疗反应性无关联。
我们的研究结果表明，SLC1A1、FAM131B和GPLD1基因多态性增加了患癫痫的风险，而FAM131B、GABRA1和CACNG5基因变异可能在预测癫痫患者（PWE）的药物反应中起作用。
